Objective — to reveal an association of I/D polymorphism of ACE gene with metabolic factors of cardiovascular risk (CVR) such as visceral obesity (VO), insulin resistance (IR), dyslipidemia (DLP) as well as with indices characterized structural and functional state of left cardiac chambers in patients (pts) with diabetic nephropathy (DN) and essential hypertension (EH). Materials and methods. The investigation was conducted at the Clinical Department of Arterial Hypertensions and Kidney Diseases in L. T. Mala National Therapy Institute of NAMS of Ukraine (Kharkiv). Clinical examinations involved 82 pts, 42 (51.2 %) females and 40 (48.8 %) males with DN of I — IV stage and EH of II — III stage, aged 31 to 82 years old (an average age is (61.65 ± 1.28) years old). Three genotypes of I/D polymorphism of ACE gene included II — 18 (24.7 %), ID — 32 (43.8 %) and DD — 23 (31.5 %) of cases correspondingly were investigated in 73 (89.0 %) pts. Anthropometric measurements with calculations of body mass index (BMI), body fat percentage (BFP), body fat mass (BFM), fat mass index (FMI) were conducted by known formulas in all pts. Blood lipids were detected by enzyme method with measuring of total cholesterol, high‑density lipoprotein cholesterol (HDL‑C) and triglycerides (TG). Levels of cholesterol of very low density and low‑density lipoprotein (VLDL‑C, LDL‑C) were calculated by standard formulas. Blood glucose level was measured by glucose oxidase method and serum insulin was detected by immunoassay method. IR indices such as HOMA‑IR, triglyceride glucose index (TGGI) and METS‑IR (metabolic score for insulin resistance) were obtained by known formulas. I/D polymorphism of ACE gene (rs 4646994) was investigated with a usage of polymerase chain reaction. Structural and functional state of left cardiac chambers was estimated using transthoracic echocardiography. Systolic and diastolic blood pressure (SBP and DBP) were measured by Korotkov’s method. The results were statistically obtained with computer programs Microsoft Office Excel 2003 and Statistica 23.0. Results. In pts with II genotype, LDL‑C levels positively correlated with BFP (r = 0.490; p = 0.046) and BFM (r = 0.484; p = 0.049) in conditions with hypertriglyceridemia due to activation of visceral fat lipolysis in which a reverse correlation between relative thickness of left ventricle wall (RTLVW) and serum TG concentration (r = –0.540; p = 0.02) could be explained. In pts with ID genotype, presence of D allele in genotype was associated with an increase in RTLVW due to SBP influence (r = 0.358; p = 0.045). In genotype ID there was a relationship between IR index HOMA‑IR and BMI (r = 0.399; p = 0.029) and HOMA‑IR and FMI (r = 0.402; p = 0.025) that demonstrated VO participation of in the development of IR in pts with DN and EH and genotype ID. In pts with DN and EH, who had DD genotype, SBP level reversely correlated with HDL‑C (r = –0.498; p = 0.018) that could be explained by influence of IR on elevation of SBP and reduction of HDL‑C. In pts with DD genotype both SBP and DBP almost equally influenced on the left atrial diameter (r = 0.460; p = 0.036 and r = 0.453; p = 0.034 correspondingly). In pts with DN and EH whose had DD genotype IR index METS‑IR positively correlated with RTLVW (r = 0.419; p = 0.047) and left ventricle myocardial mass index (r = 0.518; p = 0.011) that confirmed an association of D allele of ACE gene with left ventricle hypertrophy caused both by EH and IR. Conclusions. It has been established that in patients with diabetic nephropathy and essential hypertension, the I/D polymorphism of ACE gene was associated with such metabolic factors of cardiovascular risk as visceral obesity, insulin resistance, dyslipidemia, and pathological left ventricle remodeling.
The purpose of the study was to highlight the most studied risk factors associated with the development and/or progression of diabetic nephropathy, with an emphasis on some important aspects that should be kept in mind by the physician. Materials and methods. Research materials are publications of national and foreign authors. The methods used were: system approach and system theoretical retrospective analysis of selected materials; generalization; medical and statistical method. Results and discussion. Timely diagnostics of diabetic nephropathy and elimination of risk factors of its development and progression are emphasized to be a difficult task of clinics of internal diseases particularly in conditions when amount of these risk factors is constantly growing. The most investigated risk factors associated with development and progression of diabetic nephropathy such as age, arterial hypertension, disorders of carbohydrate and lipid exchange, proteinuria are discussed in the article. Some peculiarities of correction of metabolic risk factors such as hyperglycemia and dyslipidemia as well as hemodynamic risk factors such as arterial hypertension and intraglomerular hypertension participated in development and progression of diabetic nephropathy are discussed with consideration of acting recommendations. Some aged and gender peculiarities of change of glomerular filtration rate as well as a role of arterial hypertension in progression of diabetic nephropathy through albuminuria are considered. A significance of glycosylated hemoglobin level as an independent risk factors of microalbuminuria is demonstrated. A role of secondary lipid exchange disorders due to type 2 diabetes mellitus in reduction of glomerular filtration rate and elevation of albumin/creatinine ratio as well as albuminuria presence is emphasized. A necessity of urinal detection of nephrin and podocin levels for an early diagnostics of diabetic nephropathy and monitoring of renal glomerular dysfunction in diabetes mellitus is discussed. Some risk factors related to appearance of albuminuria as well as association of albuminuria and proteinuria with glomerular and tubular structural changes in kidney are considered. A clinical significance of albumin/creatinine ratio calculation as an alternative to daily urinal protein concentration measuring for diabetic nephropathy screening is emphasized. Some risk factors related to close positive correlation with this ratio are considered. A role of genetic factors in the development of diabetic nephropathy with a participation of known today some genes candidates and a necessity of genealogical anamnesis definition to reveal a patient’s susceptibility to development of diabetic nephropathy is discussed. Conclusion. The contemporary recommendations for control of glycemia, correction of dyslipidemia and arterial hypertension which allow significantly reduce a risk of kidney impairment in diabetes mellitus or inhibit a progression of diabetic nephropathy in patients with albuminuria and proteinuria are given. A significance of detailed investigation of principles of development and progression of diabetic nephropathy for collaboration of effective diagnostic, treatment and preventive measures is emphasized
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